This proposal's first objectives is to develop an appropriate passive electronic model of hippocampal neurons (dentate granule, CA1 and CA3 cells) using the intracellular somatic short constant current pulse technique. This technique permits estimation of the following neuronal parameters: tau m, tau l, L, and p. Also, by examining changes in the decay of the short pulse during dendritic and/or somatic conductance or capacitive change from drugs or transmitter either iontophoresed or released synaptically, the location and nature of these changes can be estimated. A neuron's electrical properties will be compared to its morphology as demonstrated by intracellular dye injection. The second objective is to use the above and more standard electrophysiological techniques to examine the effects of acute and chronic drug exposure (ethanol and pentobarbital) on the individual neurons and local circuits in the hippocampal slice. Chronic ethanol treatment of rats causes decreased dendritic arborization and decreased dendritic spines in the hippocampus as well as learning deficits. It is planned to model these "demented" neurons and to examine any changes in synaptic plasticity in the hyppocampus as parallels of memory and learning deficits. The short pulse technique permits the testing of the hypothesis that a major effect of psychoactive drugs could relate to alterations of the local distance and/or capacitance in the more peripheral dendrites of neurons. Tolerance to ethanol, a possible "learning" paradigm, has already been demonstrated in the hippocampal slice by measuring evoked responses, and it is hoped to localize the site of tolerance by intracellular recording techniques. Finally, withdrawal phenomena will be examined in the neurons and local circuits of the hippocampal and this might prove to be a useful in vitro model of withdrawal epilepsy.